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Background UK Biobank (UKB) is a large prospective cohort capturing numerous health outcomes, but limited occupational information (job title, self-reported manual work and occupational walking/standing). Aims To create and evaluate validity of a linkage between UKB and a job exposure matrix for physical work exposures based on the US Occupational Information Network (O*NET) database. Methods Job titles and UK Standard Occupational Classification (SOC) codes were collected during UKB baseline assessment visits. Using existing crosswalks, UK SOC codes were mapped to US SOC codes allowing linkage to O*NET variables capturing numerous dimensions of physical work. Job titles with the highest O*NET scores were assessed to evaluate face validity. Spearman’s correlation coefficients were calculated to compare O*NET scores to self-reported UKB measures. Results Among 324 114 participants reporting job titles, 323 936 were linked to O*NET. Expected relationships between scores and self-reported measures were observed. For static strength (0–7 scale), the median O*NET score was 1.0 (e.g. audiologists), with a highest score of 4.88 for stone masons and a positive correlation with self-reported heavy manual work (Spearman’s coefficient = 0.50). For time spent standing (1–5 scale), the median O*NET score was 2.72 with a highest score of 5 for cooks and a positive correlation with self-reported occupational walking/standing (Spearman’s coefficient = 0.56). Conclusions While most jobs were not physically demanding, a wide range of physical work values were assigned to a diverse set of jobs. This novel linkage of a job exposure matrix to UKB provides a potentially valuable tool for understanding relationships between occupational exposures and disease.

ObjectivesTo investigate the container closure integrity of a Closed System Transfer Device syringe adaptor lock in combination with disposable Luer-Lock syringes as the terminal closure device. The United Kingdom (UK) National Health Service (NHS) Pharmaceutical Quality Assurance Committee (PQAC) requires syringe integrity data for final storage devices of aseptic products such as chemotherapy drugs when prepared in advance and stored prior to use as is standard practice for dose banded drugs. The assessment comprised both physical and microbial integrity testing of the combination closed system/ Luer-Lock syringes containers at syringe sizes: 1mL, 20mL, and 50mL.MethodsIntegrity testing was performed as described in the NHS Pharmaceutical Quality Assurance Committee Yellow Cover Document 2nd edition 2013 “Protocols for the Integrity Testing of Syringes” with Chemfort™ (Simplivia, IL) syringe adaptor lock (SAL) devices as replacement for sterile blind hubs. Microbiological integrity was assessed according to Method 1 part 1.4 using Brevundimonas diminuta at 32°C for up to 14-days contact time. Two positive control devices per syringe size were tested using a blind hub cap as closure which was loosened prior to test. Physical integrity was assessed using Method 3 of the yellow cover document which is a dye intrusion method. Dye intrusion was assessed both visually and using a validated ultraviolet-visible spectrophotometer method. For each size/ batch of test articles a positive control device (n=1) was assessed using a wire wrapped around the syringe plunger tip deliberately compromising integrity. Negative controls for each size (n=1) consisted of devices not immersed in methylene blue dye.ResultsChemfort™ syringe adaptor lock/ Luer-Lock syringe combinations were shown to be: (1) free of microbiological contamination after 14-days contact time (n=60), (2) free of dye intrusion at all syringe sizes tested (n=61 in total). The data demonstrates 100% closure integrity of the final container system when Chemfort™ syringe adaptor lock replaces the syringe hub as the terminal closure device. All positive control devices demonstrated system suitability as container integrity was compromised in all positive control tests. All negative controls were negative for microbial and dye intrusion.ConclusionsSyringe adaptor lock components complied with the NHS Pharmaceutical Quality Assurance Committee Yellow Cover Document syringe integrity requirements when used as the terminal closure of Luer-Lock disposable syringes from 1mL up to 50mL. Therefore, syringe adaptor lock (Chemfort™) can be used as the terminal closure system for pre-filled syringes of chemotherapeutic drug products prepared in advance in UK NHS Pharmaceutical Technical Services.What this paper addsWhat is already known on this subjectThere is a paucity of data to support the use of closed system transfer device (CSTD) components as terminal closure devices in combination with single use leur-lock syringes in pharmaceutical technical services in the UK.A recent publication in 2020 by Marler-Hausen et al. demonstrated reduction in contamination on a UK hospital day ward when a Chemfort™ syringe adaptor CSTD components were used, providing better protection for healthworkers.National Health Service (NHS) Quality Assurance Committee Yellow Cover Document (YCD) for “Protocols for the Integrity Testing of Syringes” states container integrity data is required to support use of CSTD syringe caps in aseptic services and enabling their greater use in administration.What this study addsThis study provides the necessary integrity data for Chemfort™ (Simplivia, IL) syringe adaptor lock components in combination with syringe. Physical and microbiological integrity complied with NHS YCD requirements. Chemfort™ is the first CSTD to meet the YCD acceptance criteria allowing components to be used in aseptic services including Dose-Banding in the UK.

BACKGROUND: To transfuse blood products safely, health care workers must accurately identify patients, blood samples, and the blood components. A comprehensive bar code–based computerized tracking system was developed and implemented to identify and prevent transfusion errors. STUDY DESIGN AND METHODS: A data network, wireless devices, and bar-coded labels were pilot tested before the system was introduced hospitalwide. The system provided a complete audit trail for all transactions. Data from before and after implementation were analyzed. RESULTS: Incident reports decreased from a mean of 41.5 reports per month in the 6 months before the system was implemented to a mean of 7.2 reports per month after implementation. The blood sample rejection rate decreased from 1.82 percent to a mean of 0.17 percent after implementation. Errors detected by the new system were sorted into misscans, skipped steps, wrong steps, and prevented identification errors (PIEs). Misscans and skipped steps were the most common errors in the first 10 months after implementation. During the final transfusion step, PIEs occurred at the rate of about one per month and scans were omitted approximately 1 percent of the time. Therefore, it is estimated that mistransfusions could occur about once every 100 months on average with the new system. CONCLUSIONS: The bar code–based computerized tracking system detected and prevented identification and matching errors, thereby reducing the proportion of blood samples rejected and increasing patient safety.

The IgA-degrading metalloprotease, ZapA, of the urinary tract pathogen Proteus mirabilis is co-ordinately expressed along with other proteins and virulence factors during swarmer cell differentiation. In this communication, we have used zapA to monitor IgA protease expression during the differentiation of vegetative swimmer cells to fully differentiated swarmer cells. Northern blot analysis of wild-type cells and beta-galactosidase measurements using a zapA:lacZ fusion strain indicate that zapA is fully expressed only in differentiated swarmer cells. Moreover, the expression of zapA on nutrient agar medium is co-ordinately regulated in concert with the cycles of cellular differentiation, swarm migration and consolidation that produce the bull's-eye colonies typically associated with P. mirabilis. ZapA activity is not required for swarmer cell differentiation or swarming behaviour, as ZapA- strains produce wild-type colony patterns. ZapA- strains fail to degrade IgA and show decreased survival compared with the wild-type cells during infection in a mouse model of ascending urinary tract infection (UTI). These data underscore the importance of the P. mirabilis IgA-degrading metalloprotease in UTI. Analysis of the nucleotide sequences adjacent to zapA reveals four additional genes, zapE, zapB, zapC and zapD, which appear to possess functions required for ZapA activity and IgA proteolysis. Based on homology to other known proteins, these genes encode a second metalloprotease, ZapE, as well as a ZapA-specific ABC transporter system (ZapB, ZapC and ZapD). A model describing the function and interaction of each of these five proteins in the degradation of host IgA during UTI is presented.

All members of the genus Bordetella and Pasteurella multocida (a gram-negative bacillus genetically unrelated to Bordetella spp., yet often sharing the same ecological niche) produce a dermonecrotic toxin (DNT). The amount of toxin produced and the time required for appearance of the lesions are identical for Bordetella pertussis, B. parapertussis, and B. bronchiseptica but different for P. multocida and B. avium. DNT has been reported to act by promoting vasoconstriction; however, vasoactive compounds (verapamil, prazosin, hydralazine, tolazoline, or isoxsuprine) are able to reverse the action of the toxin only slightly. Vasoconstrictors (atropine, serotonin, epinephrine, or endothelin) did not produce DNT-like lesions. We have characterized a region of DNA essential for DNT expression. We have determined by Southern analysis that the restriction map of the DNT gene is nearly identical in B. pertussis, B. parapertussis, and B. bronchiseptica, but the sequences are not present in toxigenic B. avium and P. multocida strains. A gentamicin resistance-origin of transfer cassette cloned into a 1.8-kb NotI-BamHI fragment results in constructs which can be mobilized and recombined into the Bordetella chromosome, rendering the resultant B. pertussis, B. parapertussis, and B. bronchiseptica strains negative for DNT. A 5-kb BamHI-ApaI fragment from the B. pertussis chromosome was sequenced and revealed homology to the Escherichia coli CNF1 (cytotoxic necrotizing factor 1) toxin.

1,2,3,4-Tetrahydro-β-carboline reactant: 25 g. (0.13 mole) of tryptamine hydrochloride product: 1,2,3,4-tetrahydro-β-carboline Keywords: annulation, heterocyclic-[6]; cyclization, miscellaneous; decarboxylation

To conduct a pooled data analysis in a group of patients defined by sex, menopausal status, and underlying disease in order to examine the effect of intermittent cyclical etidronate in the prevention and treatment of corticosteroid induced osteoporosis.We selected 5 randomized, placebo controlled studies that examined the efficacy of intermittent cyclical etidronate therapy in which the raw data were available for analysis. Three were prevention studies and 2 treatment studies. The primary outcome was the difference between treatment groups in the percentage change from baseline in lumbar spine bone density. Secondary outcomes included the difference between treatment groups in the percentage change from baseline in femoral neck and trochanter bone density, and vertebral fracture rates.Results are separately pooled for the prevention and treatment studies. The prevention studies had significant mean differences (95% CI) between groups in mean percentage change from baseline in lumbar spine, femoral neck, and trochanter bone density of 3.7 (2.6 to 4.7), 1.7 (0.4 to 2.9), and 2.8% (1.3 to 4.2) after one year of treatment, in favor of the etidronate group. The treatment studies displayed a mean difference between groups in mean percentage change from baseline in lumbar spine bone density of 4.8 (2.7 to 6.9) and 5.4% (2.5 to 8.4) after one and 2 years of therapy. In the prevention studies, a reduced fracture incidence was observed in the etidronate group compared with the placebo group (relative risk 0.50; CI 0.21 to 1.19).Etidronate therapy was effective in preventing bone loss in the prevention studies and in preventing or slightly increasing bone mass in the treatment studies. A fracture benefit was observed in postmenopausal women treated with etidronate in the prevention studies.

Although physicians have the greatest influence on the resource utilization of hospital patients, Canadian hospitals have not been too successful in bringing physicians into the resource planning and decision-making processes. This is because most hospitals have been unable to provide the information needed by physicians to participate in resource management in a meaningful way. With the introduction of a new system in the Canadian Province of Alberta that fundamentally changes the way hospitals are funded, it has become even more important to involve medical staffs in the utilization management process. This article describes the new funding system and highlights some of the ways in which Wetaskiwin Health Care Centre has leveraged information technology to support the utilization management process in this new environment.

Tonoplast and Golgi ATP-driven proton pumping was measured in membrane vesicles isolated from the cortex, stele and tip of maize roots. Two nitrate-sensitive peaks of tonoplast proton pumping were detected on sucrose gradients, a light peak at 16% sucrose, believed to represent small vacuoles, and a denser peak at 25% sucrose, possibly derived from large vacuoles. The nitrate-insensitive Golgi peak occurred at 31 % sucrose. Membrane preparations of the stele and tip were active in H+-transport activity and were rich in mitochondria. In contrast, the membranes of the cortex had low levels of both ATP-driven proton pumping and mitochondrial activities. Salinity caused a doubling of the tonoplast H+-transport activity of the tip and cortex, particularly in the 25 % sucrose peak. The enhancement of the 25 % peak by salinity was correlated with an increase in vacuolation of the tip. The stelar proton pumps were only slightly stimulated by salinity. The results indicate that the cortex of maize roots is deficient in the metabolic machinery needed for vacuolar solute accumulation, but that it shows some ability to adapt to saline conditions. The physiological implications of these findings are discussed.

(1955). The Development of the Concept of Economic Man. Review of Social Economy: Vol. 13, No. 1, pp. 69-77.

Yoduro de 2, 9-dimetilo-carbolinio (DMCI) y no sus metabolitos inhibio la enzyma monoamino oxidasa y elevo14C-serotonia en el corazon e higado, pero no en el cerebro de ratas.

Mutants of Bordetella pertussis deficient in virulence-associated factors were identified by using the transposon Tn5 lac. Tn5 lac is a derivative of Tn5 which generates promoter fusions for beta-galactosidase. Tn5 lac insertions in the vir-regulated genes of B. pertussis were identified by selecting for kanamycin-resistant mutants that expressed beta-galactosidase when the vir-regulated genes were expressed but not when the vir-regulated genes were turned off. Fourteen different mutations in vir-regulated genes were identified. Two mutants were deficient in the production of the filamentous hemagglutinin, two mutants were deficient in the production of adenylate cyclase toxin and hemolysin, and one mutant was deficient in the production of dermonecrotic toxin. One insertion mapped adjacent to the pertussis toxin gene, but the mutant produced pertussis toxin. The phenotypes of the remaining eight mutants were not determined, but the mutants did not appear to be deficient in the production of the 69,000-dalton outer membrane protein (agglutinogen 3) or the capsule. Screening for mutations in either of the fimbrial genes proved to be problematic since the parental strain was found to switch from a fimbriated to a nonfimbriated state at a high frequency, which was suggestive of the metastable expression of pili in other bacteria. We used Southern blot analysis with a 30-mer specific for the fimbrial sequences. No bands with the predicted increase in size due to the 12 kilobases from Tn5 lac were observed, which suggests that none of these genes were mutated. Southern blot analysis also revealed that seven of the eight unidentified mutations mapped to different restriction fragments, which suggests that they could be deficient in as many as seven different genes.

In the search for a compound capable of selective inhibition of peripheral MAO, a number of 2,9-disubstkuted β-carbolinium compounds were synthesized. With tryptamine as the substrate, these compounds generally exerted greater inhibition of the enzyme from human liver mitochondria than that from bovine liver. An exception to this was 2-propargyl-9-methyl-β-carbolinium bromide (VII), which inhibited the enzyme from both sources to a nearly equal extent. The inhibitory activity of 2,9-dimethyl-β-carbolinium iodide (I) was further studied with mitochondrial MAO of human liver, heart, and brain; rat liver, heart, and brain; mouse liver; and bovine liver; tryptamine and tyramine were used as substrates. Compound I was more effective than pargyline in inhibiting tryptamine oxidation by human MAO from peripheral tissues but was less active than pargyline toward tyramine oxidation. Kinetic studies on the inhibition of tryptamine oxidation indicated I to be a mixed-type inhibitor with MAO from human tissues and rat liver and competitive with MAO from rat heart and brain and bovine liver. The inactivation of tryptamine oxidation by I was reversible in nature, as was VII which bears a propargyl (CH2C ≡ CH) group, the same group that endows pargyline with its irreversible binding to MAO. Since the rate of irreversible inactivation of MAO by pargyline was decreased by the presence of I, there exists the possibility of a common binding site for the two compounds.

Human subjects given C14-mescaline by mouth excrete an average of 87% of the dose during the first 24 hours and an average of 92% during the first 48 hours. Average half-life of mescaline in six hours. The composition of the urine in respect to the various metabolites of mescaline from hour to hour has been determined. The concentration of mescaline and its metabolites in the plasma and the cerebrospinal fluid at the various times has also been determined. Mescaline, 3,4,5-trimethoxyphenylacetic acid, N-acetyl-β-(3,4-dimethoxy-5-hydroxyphenyl) ethylamine and N-acetyl-mescaline have been identified in human urine after mescaline administration in the following amounts: mescaline 55–60%, 3,4,5-trimethoxyphenylacetic acid 27–30%, N-acetyl-β-(3,4,dimethoxy-5-hydroxyphenyl) ethylamine 5% and N-acetylmescaline less than 0.1%. Five other metabolites have been partially characterized. Chromatographic evidence is presented for the presence of mescaline, 3,4,5-trimethoxyphenylacetic acid, N-acetylmescaline and N-acetyl-β-(3,4-dimethoxy-5-hydroxyphenyl) ethylamine in the cerebrospinal fluid in man after oral mescaline administration.

N-Acetilmescalina fue identificada con otros metabolitos en el cerebro de las ratas despues de recibir14C-mescalina. La formacion de este metabolito acetilado se demostro incubando la mescalina radioactiva con la fraccion soluble del cerebro de las ratas. Nuestros resultados indican que el cerebro de dichos animales puede acetilar mescalina, y que la acetilacion ocurre predominantemente en la fraccion soluble.